Overdiagnosis and lives saved due to reflex testing men with intermediate prostate-specific antigen levels
Menée aux Etats-Unis à l'aide d'un modèle de microsimulation, cette étude estime le nombre de vies sauvées et la réduction du taux de surdiagnostic dus à l'utilisation de quatre tests urinaires (2:ERG, PCA3, MiPS et MiPShg) chez les hommes présentant un niveau sérique du PSA compris entre 4.0-10.0 ng/ml et âgés de 55 ou 65 ans lors du test
Background : Several prostate cancer early detection biomarkers are available for reflex testing in men with intermediate prostate-specific antigen (PSA) levels. Studies of these biomarkers typically provide information about diagnostic performance but not about overdiagnosis and lives saved, the primary drivers of associated harm and benefit.
Methods : We projected overdiagnoses and lives saved using an established microsimulation model of prostate cancer incidence and mortality with screening and treatment efficacy based on randomized trials. We used this framework to evaluate four urinary reflex biomarkers (measured in 1,112 men presenting for prostate biopsy at 10 U.S. academic/community clinics) and two hypothetical ideal biomarkers (with 100% sensitivity/specificity for any or for high-grade prostate cancer) at one-time screening tests at ages 55 and 65.
Results : Compared to biopsying all men with elevated PSA, reflex testing reduced overdiagnoses (range across ages and biomarkers = 8.8%-60.6%) but also reduced lives saved (by 7.3%-64.9%), producing similar overdiagnoses per life saved. The ideal biomarker for high-grade disease improved this ratio (by 35.2% at age 55 and 42.0% at age 65). Results were similar under continued screening for men not diagnosed at age 55, but the ideal biomarker for high-grade disease produced smaller incremental improvement.
Conclusions : Modeling is a useful tool for projecting the implications of using reflex biomarkers for long-term prostate cancer outcomes. Under simplified conditions, reflex testing with urinary biomarkers is expected to reduce overdiagnoses but also produce commensurate reductions in lives saved. Reflex testing that accurately identifies high-grade prostate cancer could improve the net benefit of screening.
Journal of the National Cancer Institute , résumé, 2018